What are the associations of Schwannoma (neurofibroma of the nerve sheath)

From the Guidelines

Schwannomas are most significantly associated with neurofibromatosis type 2 (NF2), a genetic disorder characterized by bilateral vestibular schwannomas (acoustic neuromas), as stated in the 2020 guideline on the diagnosis and treatment of vestibular schwannoma 1. The most common clinical associations of schwannomas include:

• Neurofibromatosis type 2 (NF2), a genetic disorder characterized by bilateral vestibular schwannomas (acoustic neuromas) 1
• Schwannomatosis, a distinct genetic disorder characterized by multiple schwannomas without the vestibular tumors typical of NF2 1
• Sporadic occurrence in individuals without NF2, most commonly affecting peripheral nerves in the extremities, head, neck, and flexor surfaces 1 Key characteristics of schwannomas include:
• Benign nerve sheath tumors arising from Schwann cells of peripheral, cranial, or autonomic nerves
• Histological pattern with Antoni A (densely packed cells) and Antoni B (loose myxoid tissue) areas
• Typically positive for S-100 protein on immunohistochemistry Treatment depends on location and symptoms, with surgical resection being the primary approach for symptomatic tumors, while asymptomatic lesions may be monitored with serial imaging, as recommended in the 2020 guideline on the diagnosis and treatment of vestibular schwannoma 1. In patients with NF2, bevacizumab has been shown to be a potential treatment option, with improvement of hearing and objective radiographic responses 1. The definition of NF2 is based on specific criteria, including bilateral vestibular schwannomas, family history, and presence of other NF2-related tumors, as outlined in Table 2 of the 2020 guideline on the diagnosis and treatment of vestibular schwannoma 1.

From the Research

Schwannoma Associations

• Schwannomas are associated with Neurofibromatosis Type 2 (NF2), a tumor predisposition syndrome, with approximately 5% of vestibular schwannomas related to NF2 2.
• NF2 is characterized by the development of multiple nervous system tumors, including bilateral vestibular schwannomas, due to mutation in the NF2 tumor suppressor gene 3.
• The hallmark feature of NF2 is the development of bilateral vestibular schwannomas, with nearly 100% penetrance by 60 years of age 3.
• Schwannomas also occur in other tumor predisposition syndromes, such as schwannomatosis and Carney complex 4.

Clinical Features and Treatment Options

• Vestibular schwannomas account for approximately 85% of tumors in the cerebello-pontine angle, with a lifetime incidence of approximately 1 in 1000 2.
• Management options for vestibular schwannomas include surgery, stereotactic radiation, and observation with serial imaging 2, 3.
• Early surgical intervention for vestibular schwannoma in NF2 patients is a viable management strategy to maintain hearing function and preserve facial nerve function 5.
• Recent advancements in molecular biology have led to a better understanding of the etiology and pathogenesis of vestibular schwannomas, and may lead to targeted therapies for these tumors 3.

Diagnosis and Screening

• Diagnosis of NF2 is based on clinical and genetic criteria, with mutations in the NF2 gene on chromosome 22 being the primary cause of the disease 6.
• Screening for NF2 involves regular monitoring for the development of tumors, including vestibular schwannomas, and genetic testing for mutations in the NF2 gene 6.
• The 2021 WHO Classification of Tumors of the Central Nervous System has updated the classification of schwannomas, with a focus on genetic diagnoses and the recognition of new subtypes of schwannomas 4.